Cancer cell necrosis by autoschizis: Synergism of antitumor activity of vitamin C : Vitamin K-3 on human bladder carcinoma T24 cells.

Scanning and transmission electron microscopy and fluorescence light micros copy were employed to characterize the cytotoxic effects of vitamin C (VitC ), vitamin K-3 (VitK(3)) or a VicC:VK3 combination on a human bladder carci noma cell line (T24) following I-h and 2-h vitamin treatment. T24 cells exp osed to VitC alone exhibited membranous damage (blebs and endoplasmic extru sions, elongated microvilli). VitK(3)-treated cells displayed greater membr ane damage and enucleation than those treated with VitC as well as cytoplas mic defects characteristic of cytoskeletal damage. VitC:VitK(3)-treated cel ls showed exaggerated membrane damage and an enucleation process in which t he perikarya separate from the main cytoplasmic cell body by self-excision. Self-excisions continued for perikarya which contained an intact nucleus s urrounded by damaged organelles. After further excisions of cytoplasm, the nuclei exhibited nucleolar segregation and chromatin decondensation followe d by nuclear karryorhexis and karyolysis. This process of cell death induce d by oxidative stress was named autoschizis because it showed both apoptoti c and necrotic morphologic characteristics.